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1.
Arch Gerontol Geriatr ; 127: 105586, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39096556

RESUMEN

OBJECTIVE: Insomnia is one of the most common diseases among the elderly. The elderly with long-term insomnia are more likely to have symptoms such as vertigo, fatigue, and immunity decline. Acupuncture is increasingly being used to treat insomnia. The purpose of this review is to summarize the critical acupoints in the treatment of senile insomnia and evaluate the effectiveness of the treatment. To provide a research basis for acupuncture treatment of senile insomnia in the future. METHODS: We will search the clinical studies on acupuncture in the treatment of senile insomnia published by CNKI (China National Knowledge Infrastructure), Wanfang (Wan Fang Data Knowledge Service Platform), CSTJ (China Science and Technology Journal Database), Pubmed, and ScienceDirect before December 31, 2023. Acupoint will be analyzed using TCMISS (TCM Inheritance Assistance Platform). RESULTS: 265 literatures were retrieved, and 94 were selected as the criteria. The results showed that there were 90 acupoints related to treatment. The acupoints with the highest frequency were shenmen (HT7), sanyinjiao (SP6), baihui (GV20), zusanli (ST36), neiguan (PC6), xinshu (BL15), taixi (KI3), and sishencong (EX-HN1) anmian (JLSXX-QX), shenshu (BL23). The most frequently used meridians were bladder meridian (BL), governor vessel (GV), and stomach meridian (ST). They were mainly distributed in the lower limbs and head. The most frequent specific points are the five transport points and source points. The most frequently used combinations are "shenmen (HT7) - sanyinjiao (SP6)", "shenmen (HT7) - baihui (GV20)", and "shenmen (HT7) - neiguan (PC6)". Association rule analysis showed that the acupoints with the highest confidence were shenmen (HT7), neiguan (PC6), and sanyinjiao (SP6). Network topology analysis showed that sanyinjiao (SP6), zusanli (ST36), and shenmen (HT7) were the core acupuncture points for the treatment of senile insomnia. CONCLUSION: The primary Acupuncture acupoints for senile insomnia are shenmen (HT7), sanyinjiao (SP6), baihui (GV20), zusanli (ST36), and neiguan (PC6), indicating that these acupoints have a strong correlation with senile insomnia. Sanyinjiao (SP6), zusanli (ST36), and shenmen (HT7) may be the core acupuncture acupoints for the treatment of senile insomnia.

2.
ACS Nano ; 18(32): 21091-21111, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39099105

RESUMEN

Milk exosomes (mExos) have demonstrated significant promise as vehicles for the oral administration of protein and peptide drugs owing to their superior capacity to traverse epithelial barriers. Nevertheless, certain challenges persist due to their intrinsic characteristics, including suboptimal drug loading efficiency, inadequate mucus penetration capability, and susceptibility to membrane protein loss. Herein, a hybrid vesicle with self-adaptive surface properties (mExos@DSPE-Hyd-PMPC) was designed by fusing functionalized liposomes with natural mExos, aiming to overcome the limitations associated with mExos and unlock their full potential in oral peptide delivery. The surface property transformation of mExos@DSPE-Hyd-PMPC was achieved by introducing a pH-sensitive hydrazone bond between the highly hydrophilic zwitterionic polymer and the phospholipids, utilizing the pH microenvironment on the jejunum surface. In comparison to natural mExos, hybrid vesicles exhibited a 2.4-fold enhancement in the encapsulation efficiency of the semaglutide (SET). The hydrophilic and neutrally charged surfaces of mExos@DSPE-Hyd-PMPC in the jejunal lumen exhibited improved preservation of membrane proteins and efficient traversal of the mucus barrier. Upon reaching the surface of jejunal epithelial cells, the highly retained membrane proteins and positively charged surfaces of the hybrid vesicle efficiently overcame the apical barrier, the intracellular transport barrier, and the basolateral exocytosis barrier. The self-adaptive surface properties of the hybrid vesicle resulted in an oral bioavailability of 8.7% and notably enhanced the pharmacological therapeutic effects. This study successfully addresses some limitations of natural mExos and holds promise for overcoming the sequential absorption barriers associated with the oral delivery of peptides.


Asunto(s)
Exosomas , Liposomas , Leche , Propiedades de Superficie , Animales , Administración Oral , Exosomas/química , Exosomas/metabolismo , Liposomas/química , Leche/química , Péptidos/química , Humanos , Sistemas de Liberación de Medicamentos , Ratones , Ratas Sprague-Dawley , Ratas , Masculino
3.
World Neurosurg ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39127379

RESUMEN

BACKGROUND: This bibliometric analysis aimed to map the knowledge network of laminoplasty research. METHODS: Studies on laminoplasty published from 1982 to 2023 were retrieved from the Web of Science Core Collection (WoSCC). The contributions of countries, institutions, authors, and journals were identified using VOSviewer, Scimago Graphica, and Microsoft Excel. Tendencies, hotspots and knowledge networks were analyzed and visualized using VOSviewer and CiteSpace. RESULTS: We identified 2577 publications on laminoplasty. The annual number of publications exhibited an overall increasing trend since 2004. Among these, the Japn, China and USA were the three major contributing countries. Keio University, Nagoya University, and Tokyo med & dent University were the three most productive institutions. Imagama, Shiro ranked first among authors regarding the number of articles , while Hirabayashi, K was first among co-cited authors. Spine was the top journal in terms of the number of publications, citations, and co-citations. In addition, the research topics can be divided into three clusters: 1.Comparision between laminoplasty and other surgery in outcomes and complications 2. Axial symptoms in laminoplasty 3. Sagittal alignment and sagittal balance in laminoplasty. Emerging topics sagittal alignment and sagittal balance in degenerative cervical spondylosis are identified as current research frontiers. CONCLUSION: This study drew a knowledge map of the top countries, institutions, authors, publications, and journals on laminoplasty over the past 4 decades. The current and future hotspots of laminoplasty focus on sagittal balance, comparison between other surgery in outcomes and complication and axial symptoms in laminoplasty.

4.
J Mol Biol ; : 168750, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39173734

RESUMEN

The final step in the de novo synthesis of cytidine 5'-triphosphate (CTP) is catalyzed by CTP synthase (CTPS), which can form cytoophidia in all three domains of life. Recently, we have discovered that CTPS binds to ribonucleotides (NTPs) to form filaments, and have successfully solved the structures of Drosophila melanogaster CTPS bound with NTPs. Previous biochemical studies have shown that CTPS can bind to deoxyribonucleotides (dNTPs) to produce 2'-deoxycytidine-5'-triphosphate (dCTP). However, the structural basis of CTPS binding to dNTPs is still unclear. In this study, we find that Drosophila CTPS can also form filaments with dNTPs. Using cryo-electron microscopy, we are able to solve the structure of Drosophila melanogaster CTPS bound to dNTPs with a resolution of up to 2.7 Å. By combining these structural findings with biochemical analysis, we compare the binding and reaction characteristics of NTPs and dNTPs with CTPS. Our results indicate that the same enzyme can act bifunctionally as CTP/dCTP synthase in vitro, and provide a structural basis for these activities.

5.
Adv Mater ; : e2406550, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054732

RESUMEN

A promising kind of ternary chiral co-assemblies with high PLQY, large dissymmetry factor (glum), and narrowband multi-resonance characteristics are achieved by codoped-thermal annealing treatments of achiral luminescent polymer F8BT, chiral inducers R/S-5011, and achiral FRET acceptor DBN-ICZ. The optimized co-assemblies (F8BT)0.9-(R/S-5011)0.1-(DBN-ICZ)0.005 display narrowband yellow emission with full-width half maximum (FWHM) of 37 nm, PLQY of 79%, and intense CPL signals with |glum| of up to 0.26. Meaningfully, solution-processed CP-OLEDs by using those ternary chiral co-assemblies as emitting layer are successfully fabricated, which display yellow circularly polarized electroluminescence (CPEL) with EQEmax of 4.6% and gEL of up to 0.16. The corresponding Q-factor could reach up to 7.36 × 10-3, which is the highest of all the reported CP-OLEDs. Moreover, the devices also exhibit excellent comprehensive device performance with low Von of 7.0 V, high Lmax of about 25 000 cd m-2, extremely low efficiency roll-off with EQE of 4.3% at 10 000 cd m-2, as well as narrowband EL with FWHM of only 39 nm. The proposed ternary co-assembly strategy in fabricating CP-OLED provides the possibility to achieve high comprehensive device performance such as balancing high EQE and large gEL value, as well as narrowband emission, high brightness and low efficiency roll-off simultaneously.

6.
J Glob Health ; 14: 04117, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39026457

RESUMEN

Background: The characteristics of scoliosis afflicting school children and adolescents in mainland China are still unclear. Therefore, we conducted a systematic review to estimate scoliosis's prevalence and characterise its distribution in China. Methods: We screened PubMed, Scopus, WanFang, China National Knowledge Infrastructure, National Science and Technology Library, and WeiPu databases for mainland China articles published between 1 January 1980 and 31 October 2022. Among them, we identified population-wide scoliosis studies in school children and adolescents. The main outcomes were the positive rate of primary screening and the prevalence of final screening. Primary screening mainly included general examination with/without the forward bending test in school. The final screening entailed clinical diagnosis by Röntgen radiation in a hospital (based on primary screening). A meta-analysis of scoliosis distribution by gender was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Further, we analysed the distributions of scoliosis by age, region, aetiological type, and severity of curvature, in addition to the correlation between its prevalence and altitude or latitude. Results: 77 studies with 2 224 320 participants were included. The positive rate through primary screening was 3.97%, whereas the prevalence of scoliosis at final screening was 1.20%. Analysing the data revealed a higher prevalence of scoliosis in girls (OR = 1.57; 95% CI = 1.38-1.81). The age-wise peak rate of scoliosis was 15-16 years (1.07%) in boys and 13-14 years (1.42%) in girls. The mean prevalence of scoliosis was 1.07% in the western region, 1.54% in the central, and 1.35% in the eastern. Scoliosis prevalence was not correlated with either altitude or latitude. The prevalence of idiopathic and congenital scoliosis was 1.18 and 0.03%. Among all subjects with scoliosis, 79.10 and 16.80% had mild and medium disease severity. Conclusions: According to this comprehensive study using data sets of scoliosis in adolescents across mainland China, the mean prevalence of scoliosis is 1.20%, yet 1.57 times higher in girls than boys, and is most prevalent in the middle region. Overall, scoliosis in adolescents could pose a burden to public health in mainland China. Registration: PROSPERO CRD42021231987.


Asunto(s)
Escoliosis , Adolescente , Femenino , Humanos , Masculino , China/epidemiología , Prevalencia , Escoliosis/epidemiología
7.
Sci Rep ; 14(1): 15870, 2024 07 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982153

RESUMEN

Recent studies indicate that Glypican 1 (GPC-1) is aberrantly expressed and plays a key role in certain cancers, but little is known in the hepatocellular carcinoma. Raw data from TCGA, GTEx and TIMER databases were utilized to comprehensively analyze GPC-1 expression landscape in pan-cancer, and the biological function of GPC-1 was investigated in liver cancer cells. The results revealed that GPC-1 is highly expressed in HCC, negatively correlated with survival, and also positively correlated with immune infiltration and clinical stage. Furthermore, GPC-1 promoted cell proliferation and inhibited apoptosis in the HCC cell lines. WGCNA analysis and HCCDB database revealed that Akt acted as a key molecule related to GPC-1, influencing biological functions and regulating cell malignant behaviors via the AKT signaling pathway. In conclusion, our findings provide a relatively comprehensive understanding of the oncogenic role of GPC-1 in HCC, implying that GPC-1 could serve as an innovative therapeutic target.


Asunto(s)
Carcinoma Hepatocelular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Glipicanos , Neoplasias Hepáticas , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Glipicanos/metabolismo , Glipicanos/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Línea Celular Tumoral , Apoptosis/genética , Transducción de Señal , Proteínas Proto-Oncogénicas c-akt/metabolismo
8.
Chem Commun (Camb) ; 60(63): 8240-8243, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39007923

RESUMEN

O-GlcNAcase (OGA) is implicated in several important biological and disease-relevant processes. Here, we synthesized fluorogenic probes for OGA by grafting GlcNAc directly or using a self-immolative linker to the hydroxyl position of 4-hydroxylisoindoline (BHID), a typical excited-state intramolecular proton transfer (ESIPT) probe. The probe was used for a fluorogenic assay to determine the half maximal inhibitory concentration of a known OGA inhibitor and differentiate between OGA and hexosaminidase when GlcNAc is replaced by GlcNPr, where a propionyl group is used instead of an acetyl group.


Asunto(s)
Colorantes Fluorescentes , Isoindoles , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Isoindoles/química , Isoindoles/síntesis química , Humanos , beta-N-Acetilhexosaminidasas/metabolismo , beta-N-Acetilhexosaminidasas/antagonistas & inhibidores , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Estructura Molecular , Espectrometría de Fluorescencia
9.
ACS Appl Mater Interfaces ; 16(31): 41321-41331, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39051622

RESUMEN

The clearance of urea poses a formidable challenge, and its excessive accumulation can cause various renal diseases. Urease demonstrates remarkable efficacy in eliminating urea, but cannot be reused. This study aimed to develop a composite vector system comprising microcrystalline cellulose (MCC) immobilized with urease and metal-organic framework (MOF) UiO-66-NH2, denoted as MCC@UiO/U, through the dynamic defect generation strategy. By utilizing competitive coordination, effective immobilization of urease into MCC@UiO was achieved for efficient urea removal. Within 2 h, the urea removal efficiency could reach up to 1500 mg/g, surpassing an 80% clearance rate. Furthermore, an 80% clearance rate can also be attained in peritoneal dialyzate from patients. MCC@UiO/U also exhibits an exceptional bioactivity even after undergoing 5 cycles of perfusion, demonstrating remarkable stability and biocompatibility. This innovative approach and methodology provide a novel avenue and a wide range of immobilized enzyme vectors for clinical urea removal and treatment of kidney diseases, presenting immense potential for future clinical applications.


Asunto(s)
Celulosa , Enzimas Inmovilizadas , Estructuras Metalorgánicas , Urea , Ureasa , Ureasa/química , Ureasa/metabolismo , Urea/química , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Celulosa/química , Estructuras Metalorgánicas/química , Humanos
10.
Regen Biomater ; 11: rbae045, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38845854

RESUMEN

Selective removal of ultra-high low-density lipoprotein (LDL) from the blood of hyperlipemia patients using hemoperfusion is considered an efficient method to prevent the deterioration of atherosclerotic cardiovascular disease. Based on the exceptional structure-function properties of multistimulus-responsive materials, we developed a magnetic photorenewable nanoadsorbent (Fe3O4@SiO2@Azo-COOH) with outstanding selectivity and regenerative characteristics, featuring functionalized azobenzene as the ligand. The dual-stimulus response endowed Fe3O4@SiO2@Azo-COOH with rapid separation and photoregenerative properties. The adsorbent demonstrated excellent removal efficiency of LDL with an adsorption capacity of 15.06 mg/g, and highly repetitive adsorption performance (≥5 cycles) under irradiation. Fe3O4@SiO2@Azo-COOH also exhibited remarkable adsorption properties and selectivity in human serum, with adsorption capacities of 10.93, 21.26 and 9.80 mg/g for LDL, total cholesterol and triglycerides and only 0.77 mg/g for high-density lipoprotein (HDL), resulting in a 93% selective adsorption difference (LDL/HDL). Complete green regeneration of the nanoadsorbent was achieved through a simple regeneration process, maintaining a recovery rate of 99.4% after five regeneration experiments. By combining dynamic perfusion experiment with micromagnetic microfluidics, the LDL content decreased by 16.6%. Due to its superior adsorption capacity and regenerative properties, the dual stimulus-responsive nanosorbent is considered a potential hemoperfusion adsorbent.

11.
Anal Chim Acta ; 1312: 342755, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38834267

RESUMEN

BACKGROUND: Identifying drug-binding targets and their corresponding sites is crucial for drug discovery and mechanism studies. Limited proteolysis-coupled mass spectrometry (LiP-MS) is a sophisticated method used for the detection of compound and protein interactions. However, in some cases, LiP-MS cannot identify the target proteins due to the small structure changes or the lack of enrichment of low-abundant protein. To overcome this drawback, we developed a thermostability-assisted limited proteolysis-coupled mass spectrometry (TALiP-MS) approach for efficient drug target discovery. RESULTS: We proved that the novel strategy, TALiP-MS, could efficiently identify target proteins of various ligands, including cyclosporin A (a calcineurin inhibitor), geldanamycin (an HSP90 inhibitor), and staurosporine (a kinase inhibitor), with accurately recognizing drug-binding domains. The TALiP protocol increased the number of target peptides detected in LiP-MS experiments by 2- to 8-fold. Meanwhile, the TALiP-MS approach can not only identify both ligand-binding stability and destabilization proteins but also shows high complementarity with the thermal proteome profiling (TPP) and machine learning-based limited proteolysis (LiP-Quant) methods. The developed TALiP-MS approach was applied to identify the target proteins of celastrol (CEL), a natural product known for its strong antioxidant and anti-cancer angiogenesis effect. Among them, four proteins, MTHFD1, UBA1, ACLY, and SND1 were further validated for their strong affinity to CEL by using cellular thermal shift assay. Additionally, the destabilized proteins induced by CEL such as TAGLN2 and CFL1 were also validated. SIGNIFICANCE: Collectively, these findings underscore the efficacy of the TALiP-MS method for identifying drug targets, elucidating binding sites, and even detecting drug-induced conformational changes in target proteins in complex proteomes.


Asunto(s)
Proteolisis , Humanos , Espectrometría de Masas/métodos , Lactamas Macrocíclicas/farmacología , Lactamas Macrocíclicas/química , Benzoquinonas/química , Benzoquinonas/farmacología , Temperatura , Triterpenos Pentacíclicos/química , Ciclosporina/farmacología , Ciclosporina/química , Ciclosporina/metabolismo , Estaurosporina/farmacología , Estaurosporina/metabolismo , Ligandos , Descubrimiento de Drogas , Sitios de Unión
12.
J Org Chem ; 89(13): 9672-9680, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38871666

RESUMEN

A three-component reaction of 1-(1H-indol-1-yl)isoquinolines or 1-(pyridin-2-yl)-1H-indoles, DABCO·(SO2)2, and thianthrenium salts under synergistic photoredox and palladium catalysis is accomplished. This direct C-H bond sulfonylation of indoles with the insertion of sulfur dioxide under mild conditions works efficiently, giving rise to a wide range of 2-sulfonated indoles in moderate to good yields under mild conditions. In this protocol, the generality of aryl/alkyl thianthrenium salts is demonstrated as well. A photoredox radical process combined with palladium catalysis is proposed.

13.
Int Ophthalmol ; 44(1): 233, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886282

RESUMEN

PURPOSE: Intraocular irrigating solution is extensively applied in cataract surgery. This paper explored the difference and relationship between optical coherence tomography (OCT) and optical quality analysis system (OQAS) parameters induced by compound electrolyte intraocular irrigating solution (CEIIS) or Ringer lactate (RL) solution during uncomplicated cataract surgery. METHODS: Totally 200 senior cataract patients were randomly divided into the CEIIS and RL groups (N = 100 patients/group). The anterior chamber was irrigated by CEIIS or RL during phacoemulsification. Patients were subdivided into diabetes mellitus (DM)+ and DM- groups. The central macular thickness (CMT), hyper reflective foci (HF), modulation transfer function cutoff frequency (MTF cutoff), Strehl ratio (SR), objective scatter index (OSI), and OQAS values (OVs) at 100%, 20%, and 9% contrast levels were measured preoperatively and 1 day and 1 week after operation using spectral-domain optical coherence tomography and OQAS II, respectively. Best-corrected visual acuity (BCVA) was assessed using the Snellen scale, followed by statistical analysis of its logarithm of the minimal angle of resolution. RESULTS: There were no significant differences in clinical characteristics between the CEIIS and RL groups. Both groups exhibited notably increased postoperative CMT, MTF cutoff, SR, OV at 100%, 20%, and 9% contrast levels, and reduced OSI, indicating CEIIS and RL improved postoperative visual quality. CEIIS surpassed RL solution in improving postoperative visual quality, decelerating the increase of macular HF numbers and CMT in DM+ patients and postoperative BCVA. There was no difference between CEIIS and RL in long-term vision improvement. CONCLUSION: CEIIS surpasses RL in postoperative visual recovery and retards increases of macular HF numbers and CMT in senior DM+ cataract patients.


Asunto(s)
Facoemulsificación , Lactato de Ringer , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Femenino , Masculino , Anciano , Tomografía de Coherencia Óptica/métodos , Lactato de Ringer/administración & dosificación , Facoemulsificación/métodos , Persona de Mediana Edad , Irrigación Terapéutica/métodos , Electrólitos/administración & dosificación , Recuperación de la Función , Catarata/complicaciones , Estudios Prospectivos , Soluciones Oftálmicas/administración & dosificación
14.
J Nanobiotechnology ; 22(1): 231, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720360

RESUMEN

BACKGROUND: Circulating tumor cells (CTCs) are considered as a useful biomarker for early cancer diagnosis, which play a crucial role in metastatic process. Unfortunately, the tumor heterogeneity and extremely rare occurrence rate of CTCs among billions of interfering leukocytes seriously hamper the sensitivity and purity of CTCs isolation. METHODS: To address these, we firstly used microfluidic chips to detect the broad-spectrum of triple target combination biomarkers in CTCs of 10 types of cancer patients, including EpCAM, EGFR and Her2. Then, we constructed hybrid engineered cell membrane-camouflaged magnetic nanoparticles (HE-CM-MNs) for efficient capture of heterogeneous CTCs with high-purity, which was enabled by inheriting the recognition ability of HE-CM for various CTCs and reducing homologous cell interaction with leukocytes. Compared with single E-CM-MNs, HE-CM-MNs showed a significant improvement in the capture efficiency for a cell mixture, with an efficiency of 90%. And the capture efficiency of HE-CM-MNs toward 12 subpopulations of tumor cells was ranged from 70 to 85%. Furthermore, by using HE-CM-MNs, we successfully isolated heterogeneous CTCs with high purity from clinical blood samples. Finally, the captured CTCs by HE-CM-MNs could be used for gene mutation analysis. CONCLUSIONS: This study demonstrated the promising potential of HE-CM-MNs for heterogeneous CTCs detection and downstream analysis.


Asunto(s)
Biomarcadores de Tumor , Membrana Celular , Separación Celular , Nanopartículas de Magnetita , Células Neoplásicas Circulantes , Células Neoplásicas Circulantes/patología , Células Neoplásicas Circulantes/metabolismo , Humanos , Nanopartículas de Magnetita/química , Separación Celular/métodos , Línea Celular Tumoral , Membrana Celular/metabolismo , Membrana Celular/química , Biomarcadores de Tumor/sangre , Receptor ErbB-2 , Molécula de Adhesión Celular Epitelial/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Neoplasias
15.
Transl Oncol ; 45: 101972, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38705053

RESUMEN

BACKGROUND: Accumulating evidence has shown that circular RNAs (circRNAs) are involved in gastric cancer (GC) tumorigenesis. However, specific functional circRNAs in GC remain to be discovered, and their underlying mechanisms remain to be elucidated. METHODS: CircRNAs that were differentially expressed between GC tissues and controls were analyzed using a circRNA microarray dataset. The expression of circVDAC3 in GC was determined using quantitative real-time PCR (qRT-PCR), and the structural features of circVDAC3 were validated. Cell function assays and animal experiments were conducted to explore the effects of circVDAC3 on GC. Finally, bioinformatics analysis, fluorescent in situ hybridization, and dual luciferase assays were used to analyze the downstream mechanisms of circVDAC3. RESULTS: Our results showed that circVDAC3 was downregulated in GC and inhibited the proliferation and metastasis of GC cells. Mechanistically, circVDAC3 acts as a competing endogenous RNA (ceRNA) of miR-592 and deregulates the repression of EIF4E3 by miR-592. EIF4E3 is downregulated in GC and overexpression of miR-592 or knockdown of EIF4E3 in circVDAC3-overexpressing cells weakens the anticancer effect of circVDAC3. CONCLUSION: Our study provides evidence that circVDAC3 affects the growth and metastasis of GC cells via the circVDAC3/miR-592/EIF4E3 axis. Our findings offer valuable insights into the mechanisms underlying GC tumorigenesis and suggest novel therapeutic strategies.

16.
Cell Rep ; 43(6): 114269, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38787725

RESUMEN

The 2022 mpox outbreak led the World Health Organization (WHO) to declare it a public health emergency of international concern (PHEIC). There is a need to develop more effective and safer mpox virus (MPXV)-specific vaccines in response to the mpox epidemic. The mRNA vaccine is a promising platform to protect against MPXV infection. In this study, we construct two bivalent MPXV mRNA vaccines, designated LBA (B6R-A29L) and LAM (A35R-M1R), and a quadrivalent mRNA vaccine, LBAAM (B6R-A35R-A29L-M1R). The immunogenicity and protective efficacy of these vaccines alone or in combination were evaluated in a lethal mouse model. All mRNA vaccine candidates could elicit potential antigen-specific humoral and cellular immune responses and provide protection against vaccinia virus (VACV) infection. The protective effect of the combination of two bivalent mRNA vaccines and the quadrivalent vaccine was superior to that of the individual bivalent mRNA vaccine. Our study provides valuable insights for the development of more efficient and safer mRNA vaccines against mpox.


Asunto(s)
Virus Vaccinia , Vacunas de ARNm , Animales , Virus Vaccinia/inmunología , Virus Vaccinia/genética , Ratones , Femenino , Vacunas de ARNm/inmunología , Humanos , Ratones Endogámicos BALB C , Mpox/prevención & control , Mpox/inmunología , Vaccinia/inmunología , Vaccinia/prevención & control , Anticuerpos Antivirales/inmunología , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Mensajero/inmunología , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Inmunidad Humoral
17.
Opt Lett ; 49(10): 2705-2708, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748141

RESUMEN

The silicon thermo-optic switch (TOS) is one of the most fundamental and crucial blocks in large-scale silicon photonic integrated circuits (PICs). An energy-efficient silicon TOS with ultrahigh extinction ratio can effectively mitigate cross talk and reduce power consumption in optical systems. In this Letter, we demonstrate a silicon TOS based on cascading Mach-Zehnder interferometers (MZIs) with spiral thermo-optic phase shifters. The experimental results show that an ultrahigh extinction ratio of 58.8 dB is obtained, and the switching power consumption is as low as 2.32 mW/π without silicon air trench. The rise time and fall time of the silicon TOS are about 10.8 and 11.2 µs, respectively. Particularly, the figure of merit (FOM) has been improved compared with previously reported silicon TOS. The proposed silicon TOS may find potential applications in optical switch arrays, on-chip optical delay lines, etc.

18.
ACS Biomater Sci Eng ; 10(6): 3599-3611, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38776416

RESUMEN

Accumulation of pathogenic factors in the blood may cause irreversible damage and may even be life-threatening. Hemoperfusion is an effective technique for eliminating pathogenic factors, which is widely used in the treatment of various diseases including liver failure, renal failure, sepsis, and others. Hemoperfusion adsorbents are crucial in this process as they specifically bind and remove the target pathogenic factors. This review describes the development of hemoperfusion adsorbents, detailing the different properties exhibited by inorganic materials, organic polymers, and new materials. Advances in natural and synthetic polymers and novel materials manufacturing techniques have driven the expansion of hemoperfusion adsorbents in clinical applications. Stimuli-responsive (smart responsive) adsorbents with controllable molecular binding properties have many promising and environmentally friendly biomedical applications. Knowledge gaps, future research directions, and prospects for hemoperfusion adsorbents are discussed.


Asunto(s)
Hemoperfusión , Hemoperfusión/métodos , Humanos , Adsorción , Polímeros/química , Materiales Biocompatibles/química , Animales
19.
Nat Plants ; 10(6): 880-889, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38740943

RESUMEN

In plants, the rapid accumulation of proline is a common response to combat abiotic stress1-7. Delta-1-pyrroline-5-carboxylate synthase (P5CS) is a rate-limiting enzyme in proline synthesis, catalysing the initial two-step conversion from glutamate to proline8. Here we determine the first structure of plant P5CS. Our results show that Arabidopsis thaliana P5CS1 (AtP5CS1) and P5CS2 (AtP5CS2) can form enzymatic filaments in a substrate-sensitive manner. The destruction of AtP5CS filaments by mutagenesis leads to a significant reduction in enzymatic activity. Furthermore, separate activity tests on two domains reveal that filament-based substrate channelling is essential for maintaining the high catalytic efficiency of AtP5CS. Our study demonstrates the unique mechanism for the efficient catalysis of AtP5CS, shedding light on the intricate mechanisms underlying plant proline metabolism and stress response.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Prolina/metabolismo , Complejos Multienzimáticos , Fosfotransferasas (Aceptor de Grupo Alcohol) , Glutamato-5-Semialdehído Deshidrogenasa
20.
ACS Appl Mater Interfaces ; 16(15): 19421-19431, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38568871

RESUMEN

The employment of flexible piezoresistive sensors has sparked growing interest within the realm of wearable electronic devices, specifically in the fields of health detection and e-skin. Nevertheless, the advancement of piezoresistive sensors has been impeded by their limited sensitivity and restricted operating ranges. Consequently, it is imperative to fabricate sensors with heightened sensitivity and expanded operating ranges through the utilization of the appropriate methodologies. In this paper, piezoresistive sensors were fabricated utilizing electrospun polyvinylidene fluoride/polyacrylonitrile/polyethylene-polypropylene glycol multilayer fibrous membranes anchored with polypyrrole granules as the sensing layer, while electrospun thermoplastic polyurethane (TPU) fibers were employed as the flexible substrate. The sensitivity of the sensor is investigated by varying the fiber diameter of the sensing layer. The experimental findings reveal that a concentration of 14 wt % in the spinning solution exhibits high sensitivity (996.7 kPa-1) within a wide working range (0-10 kPa). This is attributed to the favorable diameter of the fibers prepared at this concentration, which facilitates the uniform in situ growth of pyrrole. The highly deformable TPU flexible fibers and multilayer sensing layer structure enable different linear responses across a broad pressure range (0-1 MPa). Furthermore, the sensor demonstrates good cyclic stability and can detect human movements under different pressures. These results suggest that the piezoresistive sensor with a wide operating range and high sensitivity has significant potential for future health monitoring and artificial intelligence applications.

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